The immune system of the female genital tract comprises the components of mucosal (local) and systemic immune compartments. The relative contributions from these two compartments of the immune system are influenced to a different degree by biological and endocrinological factors including the menstrual cycle, use of hormonal supplements, local contraceptives, and infection. Therefore, the long-term objectives of the proposed studies are to determine the impact of such factors on the origin and transport of antibodies in female genital tract secretions, and on the B and T lymphocytes associated with the genital tissues. To address these considerations, the following specific aims are proposed: 1) to evaluate the effect of the endogenous and exogenous hormonal status on the immune system of the genital tract by measuring the levels, isotypes, and molecular forms of mucosal antibodies in cervical mucus and vaginal secretions collected from women during their menstrual cycle, in pregnancy, and in the menopause; 2) to evaluate the effect of local estrogens, spermicides, and anti-fungal agents on genital tract immunity in women during their reproductive years before and after treatment with such agents; and 3) to evaluate the relative contributions of uterine cervical and vaginal B and T cells and their products to the immune system of the genital tract before and after specific mucosal immunization. The accumulated results will provide basic information concerning the immunology of the female reproductive tract. We will ascertain the specific effects of hormones and other exogenous agents on immunoglobulin, cytokine, and secretory component expression and production in the genital tract. Rational approaches for further studies on the enhancement of immunity in the genital tract should evolve. The effects of hormonal therapy, local spermicides, and other factors on the integrity, enhancement, or suppression of the immune system of the female genital tract will be addressed in these studies.